Breast Cancer, Alzheimer’s Disease, and APOE4 Allele in the UK Biobank Cohort

Lehrer, Steven; Rheinstein, Peter H.

doi:10.3233/adr-200266

Cited by 4 publications

(1 citation statement)

References 12 publications

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“…Pluripotent stem cells enable the acquisition of a large number of neural cells to improve cell recovery after neurodegenerative disorders, such as AD or Parkinson’s disease ( 41 ). Furthermore, women with breast cancer can also have cognitive problems ( 42 ). Interestingly, there is a possible connection between sleep disorder and breast cancer ( 43 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of molecular signatures associated with sleep disorder and Alzheimer’s disease

et al. 2022

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BackgroundAlzheimer’s disease (AD) and sleep disorders are both neurodegenerative conditions characterized by impaired or absent sleep. However, potential common pathogenetic mechanisms of these diseases are not well characterized.MethodsDifferentially expressed genes (DEGs) were identified using publicly available human gene expression profiles GSE5281 for AD and GSE40562 for sleep disorder. DEGs common to the two datasets were used for enrichment analysis, and we performed multi-scale embedded gene co-expression network analysis (MEGENA) for common DEGs. Fast gene set enrichment analysis (fGSEA) was used to obtain common pathways, while gene set variation analysis (GSVA) was applied to quantify those pathways. Subsequently, we extracted the common genes between module genes identified by MEGENA and genes of the common pathways, and we constructed protein-protein interaction (PPI) networks. The top 10 genes with the highest degree of connectivity were classified as hub genes. Common genes were used to perform Metascape enrichment analysis for functional enrichment. Furthermore, we quantified infiltrating immune cells in patients with AD or sleep disorder and in controls.ResultsDEGs common to the two disorders were involved in the citrate cycle and the HIF-1 signaling pathway, and several common DEGs were related to signaling pathways regulating the pluripotency of stem cells, as well as 10 other pathways. Using MEGENA, we identified 29 modules and 1,498 module genes in GSE5281, and 55 modules and 1,791 module genes in GSE40562. Hub genes involved in AD and sleep disorder were ATP5A1, ATP5B, COX5A, GAPDH, NDUFA9, NDUFS3, NDUFV2, SOD1, UQCRC1, and UQCRC2. Plasmacytoid dendritic cells and T helper 17 cells had the most extensive infiltration in both AD and sleep disorder.ConclusionAD pathology and pathways of neurodegeneration participate in processes contributing in AD and sleep disorder. Hub genes may be worth exploring as potential candidates for targeted therapy of AD and sleep disorder.

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Section: Discussionmentioning

confidence: 99%

Identification of molecular signatures associated with sleep disorder and Alzheimer’s disease

et al. 2022

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Experiences of women with breast cancer disclosing cancer-related cognitive impairment symptoms to health professionals: a Systematic review and meta-synthesis

Hamilton,

Oxlad,

Sianis

2024

Journal of Psychosocial Oncology

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Association of white matter hyperintensities with BMD, incident fractures, and falls in the UK Biobank cohort

Cai,

Lv,

et al. 2024

Journal of Bone and Mineral Research

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Osteoporosis is the most common metabolic bone disease in the world, which increases the healthcare service burden. Recent studies have linked higher white matter hyperintensities (WMH) to reduced bone mineral density (BMD), increasing the risk of fractures and falls in older adults. However, limited evidence exists regarding the dose–response relationship between WMH and bone health in a larger and younger population. Our study aimed to examine the association of WMH volume with BMD, incident fractures and falls, with a particular focus on dose–response relationship with varying levels of WMH volume. We included 26 410 participants from the UK Biobank. The association between WMH volume and BMD was analyzed using multiple linear regression. Cox regression models were used to estimate the hazard ratios of incident fractures and falls. Restricted cubic spline (RCS) fitted for linear and Cox regression models were employed to explore potential non-linearity. Over a mean follow-up time of 3.8 years, we documented 59 hip fractures, 392 all fractures, and 375 fall incidents. When applying RCS, L-shaped relationships were identified between WMH volume and BMD across all 4 sites. Compared with those in the lowest fifth of WMH volume, the second to the highest fifths were associated with a reduction of 0.0102-0.0305 g/cm2 in femur neck BMD, 0.0075-0.0273 g/cm2 in femur troch BMD, 0.0173-0.0345 g/cm2 in lumbar spine BMD, and 0.0141-0.0339 g/cm2 in total body BMD. The association was more pronounced among women and younger participants under age 65 (Pinteraction < 0.05). Per 1 standard deviation increment of WMH volume was associated with 36.9%, 20.1%, and 14.3% higher risks of incident hip fractures, all fractures, and falls. Genetically determined WMH or APOE genotypes did not modify these associations. We demonstrated that a greater WMH was associated with BMD in a L-shaped dose–response manner, especially in women and those under 65 years.

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Breast Cancer, Alzheimer’s Disease, and APOE4 Allele in the UK Biobank Cohort

Cited by 4 publications

References 12 publications

Identification of molecular signatures associated with sleep disorder and Alzheimer’s disease

Identification of molecular signatures associated with sleep disorder and Alzheimer’s disease

Experiences of women with breast cancer disclosing cancer-related cognitive impairment symptoms to health professionals: a Systematic review and meta-synthesis

Association of white matter hyperintensities with BMD, incident fractures, and falls in the UK Biobank cohort

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